DSP-5336 absorption, metabolism, and clearance after one oral dose in advanced blood cancers

A Phase 1, Open-label Study of the Absorption, Metabolism, and Excretion of DSP-5336 Following a Single Oral Dose in Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Myeloproliferative Neoplasms

This test will see how a single oral dose of DSP-5336 (with a [14C] tracer) is absorbed, broken down, and removed from the body in adults with advanced blood cancers who have exhausted standard treatment options.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 8 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sumitomo Pharma America, Inc. (Industry-sponsored)
• Drugs / interventions: chimeric antigen receptor, radiation
• Locations: 2 sites (Chapel Hill, North Carolina and 1 other locations)
• Trial ID: NCT07444268 on ClinicalTrials.gov

What this trial studies

This Phase 1, open-label pharmacokinetic study uses a radiolabeled ([14C]) form of DSP-5336 to map absorption, metabolism, and excretion after a single oral dose. Adults with relapsed or refractory advanced hematologic malignancies who meet safety criteria will receive one dose and remain confined for intensive blood, urine, and stool collection. Timed sampling during the confinement period will characterize how the drug is absorbed, which metabolites form, and how it is eliminated. The data will guide dosing, safety monitoring, and further clinical development of DSP-5336.

Who should consider this trial

Good fit: Adults (≥18 years) with relapsed or refractory advanced hematologic malignancies, adequate liver and kidney function, ECOG performance status ≤2, and willingness to comply with confinement and specimen collection are ideal candidates.

Not a fit: Patients with acute promyelocytic leukemia, clinically significant ECG abnormalities (for example QTcF >480 ms), or those unable to comply with confinement or sample collection are unlikely to be eligible or to benefit.

Why it matters

Potential benefit: If successful, the results could clarify DSP-5336's absorption and elimination patterns and help set safe dosing and monitoring plans for later trials.

How similar studies have performed: Radiolabeled single-dose pharmacokinetic studies are a standard, widely used method to define absorption and excretion of new drugs, though DSP-5336 itself appears to be novel in this patient population.

Eligibility criteria

Inclusion Criteria:

* Male or female, of any race, ≥ 18 years of age. Female patients must be surgically sterile or postmenopausal. Male patients must be permanently sterile or agree to use contraception.
* Have an advanced hematological malignancy that is relapsed, refractory, or has progressed following receipt of standard and available treatments.
* Any prior pre-treatment toxicities resolved to ≤Grade 1 prior to enrolment, with exception of ≤Grade 2 alopecia or neuropathy.
* Adequate kidney and liver function
* ECOG performance status of ≤ 2.
* Able to attend the required study visits, including the confinement period for monitoring and collection of bowel movements and micturition.
* Able to comprehend and are willing to sign the ICF and abide by the study restrictions.

Exclusion Criteria:

* Histologic diagnosis of acute promyelocytic leukemia.
* Abnormal ECG that is clinically significant, such as QTcF \> 480 msec. QT interval correction can be performed in the case of bundle branch block.
* History of torsades de pointes.
* Left ventricular ejection fraction ≤ 45%, as determined by echocardiogram.
* Have any concurrent conditions that could pose an undue risk or interfere with interpretation of the study results, including, but not limited to clinically significant non-healing or healing wounds, concurrent congestive heart failure, unstable angina, cardiac arrhythmia requiring treatment (excluding asymptomatic atrial fibrillation), myocardial infarction within 6 months, acute coronary syndrome within 6 months, significant pulmonary disease (shortness of breath at rest or on mild exertion; eg, due to concurrent severe obstructive pulmonary disease, hypertension not controlled with concomitant medication, or diabetes mellitus with \> 2 episodes of ketoacidosis in the prior 6 months).
* History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy and hernia repair are allowed).
* History or evidence of severe dysphagia, short-gut syndrome, gastroparesis, gastrointestinal tract disease, malabsorption syndrome, the requirement for intravenous alimentation, gastric/jejunal feeds, any uncontrolled gastrointestinal disease, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally, including the inability to swallow oral medication
* Have cognitive, psychological, or psychosocial impediment that would impair their ability to receive therapy according to the protocol or would adversely affect their ability to comply with the informed consent process, protocol, or protocol-required visits and procedures.
* History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of check-in, unless approved by the investigator and medical monitor.
* Active and uncontrolled bacterial, viral, or fungal infection requiring parenteral therapy.
* Positive hepatitis panel and/or positive human immunodeficiency virus test indicative of active infection. Patients whose results are compatible with prior immunization may be included.
* Undergone HSCT, chimeric antigen receptor cell therapy, or other modified T-cell therapy within 60 days prior to dosing.
* Received donor lymphocyte infusion within 28 days prior to dosing, receiving immunosuppressive therapy post-HSCT, or have clinically active GVHD or GVHD requiring active medical intervention other than the use of topical steroids for ongoing cutaneous GVHD.
* Received systemic calcineurin inhibitors within 2 weeks prior to dosing.
* Received other anticancer drugs or other investigational treatment within 14 days or 5 half-lives, whichever is shorter, prior to dosing.
* Major surgery within 28 days prior to dosing.
* Any known intolerance or hypersensitivity to components of the study intervention.
* Patients who have previously been dosed in \> 2 radiolabeled drug studies in the last 12 months. For patients who have previously been dosed in ≤ 2 radiolabeled drug studies within the last 12 months, the previous radiolabeled dose must be at least 4 months prior to check-in to the study site where exposures are known to the investigator or 6 months prior to check-in to the study site for a radiolabeled drug study where exposures are not known to the investigator.
* Poor peripheral venous access.
* Patients with exposure to significant diagnostic or therapeutic radiation or current employment in a job requiring radiation exposure monitoring within 12 months prior to check-in.
* Patients who, in the opinion of the investigator or designee, should not participate in this study.

Where this trial is running

Chapel Hill, North Carolina and 1 other locations

• University of North Carolina — Chapel Hill, North Carolina, United States (Not_yet_recruiting)
• MD Anderson Cancer Center — Houston, Texas, United States (Recruiting)

Study contacts

• Study coordinator: Holly Beever

Conditions Advanced Hematologic Malignancies